Joia S. Mukherjee

Community-based approaches to HIV treatment in resource-poor settings

Last year, HIV surpassed other pathogens to become the world’s leading infectious cause of adult death. More than 90% of deaths occur in poor countries, yet new antiretroviral therapies have only led to a drop in AIDS deaths in industrialised countries. The main objections to the use of these agents in less-developed countries have been their high cost and the lack of health infrastructure necessary to use them. We have shown that it is possible to carry out an HIV treatment programme in a poor community in rural Haiti, the poorest country in the western hemisphere. Relying on an already existing tuberculosis-control infrastructure, we have been able to provide directly observed therapy with highly-active antiretroviral therapy (HAART) to about 60 patients with advanced HIV disease. Inclusion criteria and clinical follow-up were based on basic laboratory data available in most rural clinics. Serious side-effects have been rare and readily managed by community-health workers and clinic staff. We discuss objections to the widespread use of HAART, and suggest that directly-observed therapy of chronic infectious disease with multidrug regimens can be highly effective in settings of great privation as long as there is sustained commitment to uninterrupted care that is free to the patient. Why AIDS prevention alone is insufficient The dimensions of the global HIV crisis are such that predictions termed alarmist a decade ago are now revealed as sober projections. 1

Comprehensive Treatment of Extensively Drug-Resistant Tuberculosis

BACKGROUND Extensively drug-resistant tuberculosis has been reported in 45 countries, including countries with limited resources and a high burden of tuberculosis. We describe the management of extensively drug-resistant tuberculosis and treatment outcomes among patients who were referred for individualized outpatient therapy in Peru. METHODS A total of 810 patients were referred for free individualized therapy, including drug treatment, resective surgery, adverse-event management, and nutritional and psychosocial support. We tested isolates from 651 patients for extensively drug-resistant tuberculosis and developed regimens that included five or more drugs to which the infecting isolate was not resistant. RESULTS Of the 651 patients tested, 48 (7.4%) had extensively drug-resistant tuberculosis; the remaining 603 patients had multidrug-resistant tuberculosis. The patients with extensively drug-resistant tuberculosis had undergone more treatment than the other patients (mean [+/-SD] number of regimens, 4.2+/-1.9 vs. 3.2+/-1.6; P<0.001) and had isolates that were resistant to more drugs (number of drugs, 8.4+/-1.1 vs. 5.3+/-1.5; P<0.001). None of the patients with extensively drug-resistant tuberculosis were coinfected with the human immunodeficiency virus (HIV). Patients with extensively drug-resistant tuberculosis received daily, supervised therapy with an average of 5.3+/-1.3 drugs, including cycloserine, an injectable drug, and a fluoroquinolone. Twenty-nine of these patients (60.4%) completed treatment or were cured, as compared with 400 patients (66.3%) with multidrug-resistant tuberculosis (P=0.36). CONCLUSIONS Extensively drug-resistant tuberculosis can be cured in HIV-negative patients through outpatient treatment, even in those who have received multiple prior courses of therapy for tuberculosis.

Programmes and principles in treatment of multidrug-resistant tuberculosis

Multidrug-resistant tuberculosis (MDR-TB) presents an increasing threat to global tuberculosis control. Many crucial management issues in MDR-TB treatment remain unanswered. We reviewed the existing scientific research on MDR-TB treatment, which consists entirely of retrospective cohort studies. Although direct comparisons of these studies are impossible, some insights can be gained: MDR-TB can and should be addressed therapeutically in resource-poor settings; starting of treatment early is crucial; aggressive treatment regimens and high-end dosing are recommended given the lower potency of second-line antituberculosis drugs; and strategies to improve treatment adherence, such as directly observed therapy, should be used. Opportunities to treat MDR-TB in developing countries are now possible through the Global Fund to Fight AIDS, TB, and Malaria, and the Green Light Committee for Access to Second-line Anti-tuberculosis Drugs. As treatment of MDR-TB becomes increasingly available in resource-poor areas, where it is needed most, further clinical and operational research is urgently needed to guide clinicians in the management of this disease.

Multidrug-resistant tuberculosis management in resource-limited settings.

Managing MDRTB through national programs can yield results similar to those seen in wealthier settings.

Treatment of extensively drug-resistant tuberculosis in Tomsk, Russia: a retrospective cohort study

BACKGROUND Mycobacterium tuberculosis strains that cause untreatable drug-resistant disease are a threat worldwide. We describe the treatment, management, and outcomes of patients with extensively drug-resistant tuberculosis in Tomsk, Russia. METHODS We undertook a retrospective cohort study of 608 patients with multidrug resistant tuberculosis who had treatment in civilian or prison services, between Sept 10, 2000, and Nov 1, 2004, according to the treatment strategy recommended by WHO. Clinical characteristics, management practices, and treatment outcomes of patients with extensively drug-resistant (XDR) tuberculosis and non-extensively drug-resistant (non-XDR) tuberculosis are described. The main outcome was the frequency of poor and favourable outcomes at the end of treatment. FINDINGS Of 608 patients with multidrug resistant tuberculosis, 29 (4.8%) patients had baseline XDR tuberculosis. Treatment failure was more common in patients with XDR tuberculosis than in those with non-XDR tuberculosis (31%vs 8.5%, p=0.0008). 48.3% of patients with XDR tuberculosis and 66.7% of patients with non-XDR tuberculosis had treatment cure or completion (p=0.04). The frequency and management of adverse events did not differ between patients with XDR and non-XDR tuberculosis. INTERPRETATION The chronic features of tuberculosis in these patients suggest that extensively drug-resistant tuberculosis may be acquired through previous treatments that include second-line drugs. Aggressive management of this infectious disease is feasible and can prevent high mortality rates and further transmission of drug-resistant strains of Mycobacterium tuberculosis.

Excellent clinical outcomes and high retention in care among adults in a community-based HIV treatment program in rural Rwanda.

Background: Access to antiretroviral therapy (ART) has rapidly expanded; as of the end of 2010, an estimated 6.6 million people are receiving ART in low-income and middle-income countries. Few reports have focused on the experiences of rural health centers or the use of community health workers. We report clinical and programatic outcomes at 24 months for a cohort of patients enrolled in a community-based ART program in southeastern Rwanda under collaboration between Partners In Health and the Rwandan Ministry of Health. Methods and Findings A retrospective medical record review was performed for a cohort of 1041 HIV+ adult patients initiating community-based ART between June 1, 2005, and April 30, 2006. Key programatic elements included free ART with direct observation by community health worker, tuberculosis screening and treatment, nutritional support, a transportation allowance, and social support. Among 1041 patients who initiated community-based ART, 961 (92.3%) were retained in care, 52 (5%) died and 28 (2.7%) were lost to follow-up. Median CD4 T-cell count increase was 336 cells per microliter [interquartile range: (IQR): 212–493] from median 190 cells per microliter (IQR: 116–270) at initiation. Conclusions: A program of intensive community-based treatment support for ART in rural Rwanda had excellent outcomes in 24-month retention in care. Having committed to improving access to HIV treatment in sub-Saharan Africa, the international community, including country HIV programs, should set high programmatic outcome benchmarks.

From directly observed therapy to accompagnateurs: enhancing AIDS treatment outcomes in Haiti and in Boston.

Like tuberculosis, human immunodeficiency virus (HIV) disease is associated with poverty and social inequalities, conditions that hamper the delivery of care. Like tuberculosis, treatment of HIV infection requires multidrug regimens, and the causative agent acquires drug resistance, which can be transmitted to others. A pilot project in rural Haiti introduced DOT-HAART (directly observed therapy with highly active antiretroviral therapy) for the care of patients with advanced acquired immune deficiency syndrome. A similar DOT-HAART effort was launched in Boston for patients with drug-resistant HIV disease who had experienced failure of unsupervised therapy. In both settings, community health promoters or accompagnateurs provide more than DOT: they offer psychosocial support and link patients to clinical staff and available resources. DOT-HAART in these 2 settings presents both challenges and opportunities. These models of care can be applied to other poverty-stricken populations in resource-poor settings.

Strategies for Harm Reduction Among HIV-Affected Couples Who Want to Conceive

As effective HIV treatments become more widespread, HIV-infected individuals are living longer, healthier lives. Many HIV-affected couples (sero-discordant and sero-concordant) are considering options for safer reproduction. A large body of evidence suggests that reproductive technologies can help HIV-affected couples to safely conceive with minimal risk of HIV transmission to their partner. However, for most couples such technologies are neither geographically nor economically accessible. This paper addresses the options for safer procreation among HIV-affected couples who cannot access reproductive technologies.

An information system and medical record to support HIV treatment in rural Haiti.

Lack of infrastructure, including information and communication systems, is considered a barrier to successful HIV treatment programmes in resource poor areas. The authors describe how they set up a web based medical record system linking remote areas in rural Haiti and how it is used to track clinical outcomes, laboratory tests, and drug supplies and to create reports for funding agencies

Rwanda 20 years on: investing in life

Two decades ago, the genocide against the Tutsis in Rwanda led to the deaths of 1 million people, and the displacement of millions more. Injury and trauma were followed by the effects of a devastated health system and economy. In the years that followed, a new course set by a new government set into motion equity-oriented national policies focusing on social cohesion and people-centred development. Premature mortality rates have fallen precipitously in recent years, and life expectancy has doubled since the mid-1990s. Here we reflect on the lessons learned in rebuilding Rwandas health sector during the past two decades, as the country now prepares itself to take on new challenges in health-care delivery.